Effect of mechanical ventilation during cardiopulmonary bypass on end-expiratory lung volume in the perioperative period of cardiac surgery: an observational study.

BACKGROUND: Many studies explored the impact of ventilation during cardiopulmonary bypass (CPB) period with conflicting results. Functional residual capacity or End Expiratory Lung Volume (EELV) may be disturbed after cardiac surgery but the specific effects of CPB have not been studied. Our objective was to compare the effect of two ventilation strategies during CPB on EELV. METHODS: Observational single center study in a tertiary teaching hospital. Adult patients undergoing on-pump cardiac surgery by sternotomy were included. Maintenance of ventilation during CPB was left to the discretion of the medical team, with division between "ventilated" and "non-ventilated" groups afterwards. Iterative intra and postoperative measurements of EELV were carried out by nitrogen washin-washout technique. Main endpoint was EELV at the end of surgery. Secondary endpoints were EELV one hour after ICU admission, PaO2/FiO2 ratio, driving pressure, duration of mechanical ventilation and post-operative pulmonary complications. RESULTS: Forty consecutive patients were included, 20 in each group. EELV was not significantly different between the ventilated versus non-ventilated groups at the end of surgery (1796 ± 586 mL vs. 1844 ± 524 mL, p = 1) and one hour after ICU admission (2095 ± 562 vs. 2045 ± 476 mL, p = 1). No significant difference between the two groups was observed on PaO2/FiO2 ratio (end of surgery: 339 ± 149 vs. 304 ± 131, p = 0.8; one hour after ICU: 324 ± 115 vs. 329 ± 124, p = 1), driving pressure (end of surgery: 7 ± 1 vs. 8 ± 1 cmH2O, p = 0.3; one hour after ICU: 9 ± 3 vs. 9 ± 3 cmH2O), duration of mechanical ventilation (5.5 ± 4.8 vs 8.2 ± 10.0 h, p = 0.5), need postoperative respiratory support (2 vs. 1, p = 1), occurrence of pneumopathy (2 vs. 0, p = 0.5) and radiographic atelectasis (7 vs. 8, p = 1). CONCLUSION: No significant difference was observed in EELV after cardiac surgery between not ventilated and ventilated patients during CPB.

COVID-19 in a patient implanted with a total artificial heart: a case report.

Background: The coronavirus disease 2019 (COVID-19) was first identified in December 2019 and is currently still a public health issue affecting millions of people worldwide. Heart failure patients are known to be at higher risk of morbidity and mortality in this case. Yet, few data exist concerning COVID-19 among patients with a left ventricular assistance device, and even less among those with a total artificial heart (TAH). Case summary: A 27-year-old man with Marfan syndrome underwent prophylactic ascending aorta replacement. Shortly after surgery completion, he developed refractory cardiogenic shock with biventricular dysfunction leading to veno-arterial extracorporeal membrane oxygenation (VA-ECMO) implantation. In the context of no appropriate eligible donor during the following 10 days while waiting on the heart transplantation list, the patient was scheduled for a TAH as a bridge to transplantation. Meanwhile, he developed an acute respiratory distress syndrome secondary to SARS-CoV-2. The patient was successfully treated with corticosteroids, prone positioning and mechanical ventilation, and heart transplantation occurred 5 weeks after COVID-19 onset. Discussion: Here, we report the first case of a patient presenting with COVID-19 infection following TAH implantation in a bridge to transplantation. We highlight that (i) cardiogenic shock patients simultaneously infected by COVID-19 should be treated instantly with all-time available technology to ensure best outcomes, including TAH and prone positioning, (ii) heart transplantation safety 5 weeks after COVID-19 onset.

Predictors of Clinical Success After Transcatheter Paravalvular Leak Closure: An International Prospective Multicenter Registry.

BACKGROUND: Transcatheter closure of a symptomatic prosthetic paravalvular leak (PVL) is feasible, but there is presently no conclusive evidence to show consistent efficacy. We aimed to identify predictors of clinical success after transcatheter PVL closure. METHODS: Consecutive patients referred to 24 European centers for transcatheter PVL closure in 2017 to 2019 were included in a prospective registry (Fermeture de Fuite ParaProthétique, FFPP). Clinical success was absence of any of the following within 1 month: re-admission for heart failure, blood transfusion, open-heart valvular surgery, and death. RESULTS: We included 216 symptomatic patients, who underwent 238 percutaneous PVL closure procedures on the mitral (64.3%), aortic (34.0%), or tricuspid (1.7%) valve. Symptoms were heart failure, hemolytic anemia, or both in 48.9%, 7.8%, and 43.3% of patients, respectively. One, 2, and 3 leaks were treated during the same procedure in 69.6%, 26.6%, and 3.8% of patients, respectively. The PVL was pinpoint or involved 1/8 or 1/4 of the valve circumference in 18.6%, 52.4%, and 28.1% of cases, respectively. The most frequently used devices were the Vascular Plug 3, Ventricular Septal Defect Occluder, Vascular Plug 2, and Paravalvular Leak Device (45.0%, 16.6%, 14.2%, and 13.6% of cases, respectively). Successful device(s) implantation with leak reduction to ≤grade 2 was obtained in 85.0% of mitral and 91.4% of aortic procedures, respectively (P=0.164); with major periprocedural adverse event rates of 3.3% and 1.2%, respectively (P=0.371); and clinical success rates of 70.3% and 88.0%, respectively (P=0.004). By multivariate analysis, technical failure, mechanical valve, and hemolytic anemia were independently associated with absence of clinical success (odds ratios [95% CIs], 7.7 [2.0-25.0]; P=0.002; 3.6 [1.1-11.1]; P=0.036; and 3.7 [1.2-11.9]; P=0.025; respectively). CONCLUSIONS: Transcatheter PVL closure is efficient and safe in symptomatic patients but is associated with a lower clinical success rate in patients with hemolysis and/or a mechanical valve. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifiers: NCT05089136.

Cardiovascular outcomes of patients treated for non-Hodgkin lymphoma with first-line doxorubicin-based chemotherapy.

We conducted a single-center retrospective study to assess cardiovascular (CV) toxicity and treatment discontinuation for CV toxicity in diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) patients treated with immunochemotherapy (R-CHOP-like). Between 2006 and 2017, 433 patients were included (DLBCL: n = 345, FL: n = 88). The median age was 63 years (50-73). We defined three types of CV toxicity: early-onset cardiovascular toxicity (the event occurred within 6 months following treatment start); subacute toxicity (the event occurred between 6 months and 1 year after treatment start) and late toxicity (the event occurred 1 year or more after treatment start). Forty-eight (11.1%) patients experienced at least one anthracycline-related CV event. Seven patients experienced treatment discontinuation due to CV toxicity. Early-onset and subacute cardiac events were primarily acute heart failure (34.3%) and atrial fibrillation (28.6%). History of ischemic heart disease (p = 0.02) and valvular heart disease (p = 0.03) were associated with a higher risk of anthracycline-related CV event occurrence.

Reliability of the Minto model for target-controlled infusion of remifentanil during cardiac surgery with cardiopulmonary bypass.

BACKGROUND: The Minto pharmacokinetic model is used for target-controlled infusion of remifentanil. The reliability of this model has never been evaluated during normothermic cardiac surgery with cardiopulmonary bypass (CPB). The aim of this study was to assess the predictive performance of the model during CPB to determine its reliability during cardiac surgery. METHODS: This was a single-centre observational study. Arterial blood samples were drawn at five time points: T1, after tracheal intubation; T2, immediately before CPB; T3, 10 min after starting CPB; T4, 45 min after starting CPB; T5, 10 min after weaning off CPB. Prediction error (PE) and absolute prediction error (APE) were calculated for each sample and used to determine median prediction error (MDPE) and median absolute prediction error (MDAPE) per patient. Risk factors for APE >30% were assessed using multivariable analysis. Results are presented as medians with inter-quartile ranges. RESULTS: Fifty-eight patients with 283 blood samples (110 during CPB) were included. In the pre-CPB period, MDPE and MDAPE were -17.3 [-32.9 to 2.3] and 24.6 [12-37.7]%, whereas during CPB, they were -1.8 [-15.6 to 11.1] and 14.0 [6.74-27.1]%, respectively. There was no statistically significant difference between measured and predicted remifentanil plasma concentrations during CPB. Age, preoperative albumin concentrations, temperature, and haemodilution were not independently associated with MDAPE >30%. CONCLUSIONS: The Minto model accurately predicts plasma remifentanil concentrations during cardiac surgery with CPB. CLINICAL TRIAL REGISTRATION: 2017-A03153-50.

ACURATE neo™ aortic valve implantation via carotid artery access: first case report.

BACKGROUND: The ACURATE neo™ transcatheter heart valve (Boston Scientific, Marlborough, Massachusetts) is predominantly implanted via femoral access. Transcarotid use of this prothesis has never been reported. CASE PRESENTATION: We present the case of an 89-year-old woman referred to us for a transcatheter aortic valve replacement (TAVR). After apparatus imaging of the aortic annulus and the peripheral vascular pathway, the heart team was confronted with a triple challenge: (i) The preferable choice of a self-expanding valve because of a small aortic annulus in an obese woman. (ii) Gaining favorable access to the coronary ostia, considering multiple recent coronary stenting. (iii) Utilizing an alternative arterial access because of iliac and femoral severely calcified stenosis. Implanting the ACURATE neo™ transcatheter heart valve (THV) via carotidal access allowed us to overcome these challenges. The procedure was performed successfully without any short-term complications. CONCLUSION: We report the first case of implantation of an ACURATE neo™ transcatheter heart valve (Boston Scientific, Marlborough, Massachusetts) via the right common carotid artery.

Single-source dual energy CT to assess myocardial extracellular volume fraction in aortic stenosis before transcatheter aortic valve implantation (TAVI).

PURPOSE: To assess myocardial extracellular volume fraction (ECV) measurement provided by a single-source dual-energy computed tomography (SSDE-CT) acquisition added at the end of a routine CT examination before transcatether aortic valve implantation (TAVI) compared to cardiac magnetic resonance imaging (MRI). MATERIALS AND METHODS: Twenty-one patients (10 men, 11 women; mean age, 86±4.9 years [SD]; age range: 71-92 years) with severe aortic stenosis underwent standard pre-TAVI CT with additional cardiac SSDE-CT acquisition 7minutes after intravenous administration of iodinated contrast material and myocardial MRI including pre- and post-contrast T1-maps. Myocardial ECV and standard deviation (σECV) were calculated in the 16-segments model. ECV provided by SSDE-CT was compared to ECV provided by MRI, which served as the reference. Analyses were performed on a per-segment basis and on a per-patient involving the mean value of the 16-segments. RESULTS: ECV was slightly overestimated by SSDE-CT (29.9±4.6 [SD] %; range: 20.9%-48.3%) compared to MRI (29.1±3.9 [SD] %; range: 22.0%-50.7%) (P<0.0001) with a bias and limits of agreement of +2.3% (95%CI: -16.1%-+20.6%) and +2.5% (95%CI: -2.1%-+7.1%) for per-segment and per-patient-analyses, respectively. Good (r=0.81 for per-segment-analysis) to excellent (r=0.97 for per-patient-analysis) linear relationships (both P<0.0001) were obtained. The σECV was significantly higher at SSDE-CT (P<0.0001). Additional radiation dose from CT was 1.89±0.38 (SD) mSv (range: 1.48-2.47 mSv). CONCLUSION: A single additional SSDE-CT acquisition added at the end of a standard pre-TAVI CT protocol can provide ECV measurement with good to excellent linear relationship with MRI.

Direct measurement of cardiac stiffness using echocardiographic shearwave imaging during open-chest surgery: A pilot study in human.

PURPOSE: Cardiac stiffness is a marker of diastolic function with a strong prognostic significance in many heart diseases that is not measurable in clinical practice. This study investigates whether elastometry, a surrogate for organ stiffness, is measurable in the heart using ShearWave Imaging. METHODS: In 33 anesthetized patients scheduled for cardiac surgery, ShearWave imaging was acquired epicardially using a dedicated ultrasound machine on the left ventricle parallel to the left anterior descending coronary artery in a loaded heart following the last cardiac beat. Cardiac elastometry was measured offline using the Young modulus with customized software. RESULTS: Overall, the ejection fraction was 61 ± 10%. E/A and E/e' ratios were 1.0 ± 0.5 and 10.5 ± 4.1, respectively. Cardiac elastometry averaged 15.3 ± 5.3 kPa with a median of 18 kPa. Patients with high elastometry >18 kPa were older (P = .04), had thicker (P = .02) but smaller LV (P = .004), had larger left atria (P = .05) and a higher BNP level (P = .04). We distinguished three different transmural elastometry patterns: higher epicardial, higher endocardial, or uniformly distributed elastometry. CONCLUSION: Elastometry measurement was feasible for the human heart. This surrogate for cardiac stiffness dichotomized patients with low and high elastometry, and provided three different phenotypes of transmural elastometry with link to diastolic function.

Phenotype and Outcomes of Pulmonary Hypertension Associated with Neurofibromatosis Type 1.

Rationale: Pulmonary hypertension (PH) associated with neurofibromatosis type 1 (NF1) is a rare and largely unknown complication of NF1.Objectives: To describe characteristics and outcomes of PH-NF1.Methods: We reported the clinical, functional, radiologic, histologic, and hemodynamic characteristics, response to pulmonary arterial hypertension (PAH)-approved drugs, and transplant-free survival of patients with PH-NF1 from the French PH registry.Measurements and Main Results: We identified 49 PH-NF1 cases, characterized by a female/male ratio of 3.9 and a median (minimum-maximum) age at diagnosis of 62 (18-82) years. At diagnosis, 92% were in New York Heart Association functional class III or IV. The 6-minute-walk distance was 211 (0-460) m. Pulmonary function tests showed low DlCO (30% [12-79%]) and severe hypoxemia (PaO2 56 [38-99] mm Hg). Right heart catheterization showed severe precapillary PH with a mean pulmonary artery pressure of 45 (10) mm Hg and a pulmonary vascular resistance of 10.7 (4.2) Wood units. High-resolution computed tomography images revealed cysts (76%), ground-glass opacities (73%), emphysema (49%), and reticulations (39%). Forty patients received PAH-approved drugs with a significant improvement in functional class and hemodynamic parameters. Transplant-free survival at 1, 3, and 5 years was 87%, 54%, and 42%, respectively, and four patients were transplanted. Pathologic assessment showed nonspecific interstitial pneumonia and major pulmonary vascular remodeling.Conclusions: PH-NF1 is characterized by a female predominance, a low DlCO, and severe functional and hemodynamic impairment. Despite a potential benefit of PAH treatment, prognosis remains poor, and double-lung transplantation is an option for eligible patients.

Midterm procedural and clinical outcomes of percutaneous paravalvular leak closure with the Occlutech Paravalvular Leak Device.

AIMS: The aim of this study was to assess the efficacy and safety of the Occlutech Paravalvular Leak Device (PLD) for the percutaneous closure of paravalvular leaks (PVL). METHODS AND RESULTS: Patients with PVL were enrolled at 21 sites from nine countries. Indications for PVL closure were heart failure and/or haemolytic anaemia. Endpoint measures were changes in PV regurgitation grade, NYHA class and requirement for haemolysis-related transfusion. One-hundred and thirty-six patients with mitral (67.6%) or aortic (32.4%) leaks were included (mean age 66.7 years, 58% male); 31% had multiple PVLs. The proportion of patients with NYHA Class III/IV decreased from 77.3% at baseline to 16.9% at latest follow-up. The proportion of patients with need for haemolysis-related blood transfusion decreased from 36.8% to 5.9% and from 8.3% to 0% for ML patients and AL patients, respectively. All-cause mortality was 7.4%. Complications included interference with valve leaflets (0.7%), transient device embolisation (percutaneously solved) (0.7%), late device embolisation (0.7%), recurrent haemolytic anaemia (2.2%), new-onset haemolytic anaemia (0.7%), valve surgery (2.2%), need for repeat closure (0.7%), complications at femoral puncture site (0.7%) and arrhythmias requiring treatment (4.4%). CONCLUSIONS: PVL closure with the Occlutech PLD demonstrated a high success rate associated with significant clinical improvement and a relatively low rate of serious complications. Visual summary. PVL characteristics, leak approach, device types and midterm procedural and clinical outcomes of percutaneous paravalvular leak closure with the Occlutech® PLD. Transcatheter PVL closure with the specifically designed PLD was demonstrated to be effective with a relatively low rate of major complications. Procedural success for ML and AL closure was high with a low rate of residual or recurrent leaks. Significant improvement of NYHA class, and reduction of haemolytic anaemia and transfusion dependency were achieved.

Light chain lambda myeloma with fatal AL cardiac amyloidosis in a 21-year-old patient: A case report and review.

Multi-organ AL amyloidosis is a therapeutic challenge because of light chain deposits severely damaging the function of concerned organs. Cardiac involvement, which leads to concentric hypertrophy of both ventricles, is particularly severe and leads to poor prognosis regardless of combination chemotherapy. This case pinpoints the relevance of combining clinical, histological, and echocardiographic information in the management of this complex and life-threatening disease.

Incidence, Prognostic Impact, and Predictive Factors of Readmission for Heart Failure After Transcatheter Aortic Valve Replacement.

OBJECTIVES: The aim of this study was to assess the incidence, prognostic impact, and predictive factors of readmission for congestive heart failure (CHF) in patients with severe aortic stenosis treated by transcatheter aortic valve replacement (TAVR). BACKGROUND: TAVR is indicated in patients with severe symptomatic aortic stenosis in whom surgery is considered high risk or is contraindicated. Readmission for CHF after TAVR remains a challenge, and data on prognostic and predictive factors are lacking. METHODS: All patients who underwent TAVR from January 2010 to December 2014 were included. Follow-up was achieved for at least 1 year and included clinical and echocardiographic data. Readmission for CHF was analyzed retrospectively. RESULTS: This study included 546 patients, 534 (97.8%) of whom were implanted with balloon-expandable valves preferentially via the transfemoral approach in 87.8% of cases. After 1 year, 285 patients (52.2%) had been readmitted at least once, 132 (24.1%) for CHF. Patients readmitted for CHF had an increased risk for death (p < 0.0001) and cardiac death (p < 0.0001) compared with those not readmitted for CHF. On multivariate analysis, aortic mean gradient (hazard ratio [HR]: 0.88; 95% confidence interval [CI]: 0.79 to 0.99; p = 0.03), post-procedural blood transfusion (HR: 2.27; 95% CI: 1.13 to 5.56; p = 0.009), severe post-procedural pulmonary hypertension (HR: 1.04; 95% CI: 1.00 to 1.07; p < 0.0001), and left atrial diameter (HR: 1.47; 95% CI: 1.08 to 2.01; p = 0.02) were independently associated with CHF readmission at 1 year. CONCLUSIONS: Readmission for CHF after TAVR was frequent and was strongly associated with 1-year mortality. Low gradient, persistent pulmonary hypertension, left atrial dilatation, and transfusions were predictive of readmission for CHF.

Single-source dual-energy CT angiography with reduced iodine load in patients referred for aortoiliofemoral evaluation before transcatheter aortic valve implantation: impact on image quality and radiation dose.

OBJECTIVES: To compare image quality and radiation dose of pre-transcatheter aortic valve implantation (TAVI) aortoiliofemoral CT angiography (AICTA) provided by standard vs. dual-energy mode with reduced iodine load protocols. METHODS: One hundred and sixty-one patients underwent a two-step CTA protocol before TAVI including cardiac CTA with injection of 65 mL of iodinated contrast agent (ICA), immediately followed by AICTA. From this second acquisition, the following three different patient groups were identified: Group 1: 52 patients with standard AICTA (60 mL ICA, 100 kVp, mA automodulation); Group 2: 48 patients with dual-energy AICTA with 50 % iodine load reduction (30 mL ICA, fast kVp switching, 600 mA); Group 3: 61 patients with an identical protocol to Group 2, but exposed to 375 mA. The qualitative/subjective image quality (13-point score) and quantitative/objective image quality (contrast attenuation and image noise) were evaluated. The radiation dose was recorded. RESULTS: There was no significant difference in non-diagnostic images between the three protocols. Contrast attenuation, signal-to-noise ratio and contrast-to-noise ratio were significantly higher, whereas noise was significantly lower in the standard protocol (all P < 0.05). The radiation dose was lower in the dual-energy protocol at 375 mA (P < 0.05). CONCLUSIONS: Dual-energy AICTA before TAVI results in a reduction of iodine load while maintaining sufficient diagnostic information despite increased noise. KEY POINTS: • Dual-energy AICTA before TAVI results in a 50 % reduction of iodine load. •The reduction of iodine load maintains sufficient image quality despite increased noise. • Using 375 mA in dual-energy mode results in a reduction of radiation dose. • A high tube current setting (600 mA) should be used in overweight patients.

Patients with severe aortic stenosis and reduced ejection fraction: earlier recovery of left ventricular systolic function after transcatheter aortic valve implantation compared with surgical valve replacement.

BACKGROUND: Only 50% of patients with aortic stenosis (AS) and low ejection fraction (EF) improve their contractility after surgical aortic valve replacement (AVR). Long-term prognosis of these patients is strongly correlated to EF recovery after the surgery. The aim of this study was to compare the postoperative left ventricular function recovery in patients with severe AS and reduced EF after AVR and transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: Twenty-one patients undergoing AVR for severe AS (<1 cm²) and reduced EF (<45%) were echocardiographically compared with 31 patients treated with TAVI by conventional and two-dimensional (2D) strain method. TAVI patients were older (83 ± 6 vs. 74 ± 13 years, P < 0.001), had more comorbidities (Euroscore 26 ± 15% vs. 16 ± 12%, P < 0.001) and no differences in ischemic heart disease (16.1% vs. 9.5%, P = 0.39). EF was similar in both groups at baseline. Aortic valve area significantly increased (P = 0.01) while pressure gradient decreased (P = 0.009) after both procedures but TAVI was associated with a better EF recovery compared with AVR at day 7. Regional function assessed by radial 2D strain increased in TAVI group but was transiently deteriorated in AVR patients (P < 0.05). Longitudinal as well as circumferential 2D strain progressively increased at follow-up in both groups (P < 0.05). EF was similar in both groups at 3-month follow-up. CONCLUSION: In patients with severe AS and reduced EF, TAVI is associated with faster and better recovery of LV function compared with AVR.

Performance analysis of EuroSCORE II compared to the original logistic EuroSCORE and STS scores for predicting 30-day mortality after transcatheter aortic valve replacement.

The original European System for Cardiac Operative Risk Evaluation (EuroSCORE) has been recently updated as EuroSCORE II to optimize its efficacy in cardiac surgery, but its performance has been poorly evaluated for predicting 30-day mortality in patients who undergo transcatheter aortic valve replacement (TAVR). Consecutive patients (n = 250) treated with TAVR were included in this analysis. Transapical access was used in 60 patients, while 190 procedures were performed using a transfemoral approach. Calibration (risk-adjusted mortality ratio) and discrimination (C-statistic and U-statistic) were calculated for the logistic EuroSCORE, EuroSCORE II, and Society of Thoracic Surgeons (STS) scores for predicting 30-day mortality. Observed mortality was 7.6% in the overall population (6.3% and 11.7% for the transfemoral and transapical cohorts, respectively). Predicted mortality was 22.6 ± 12.8% by logistic EuroSCORE, 7.7 ± 5.8% by EuroSCORE II, and 7.3 ± 4.1% by STS score. The risk-adjusted mortality ratio was 0.34 (95% confidence interval [CI] 0.10 to 0.58) for logistic EuroSCORE, 0.99 (95% CI 0.29 to 1.69) for EuroSCORE II, and 1.05 (95% CI 0.30 to 1.79) for STS score. Moderate discrimination was observed with EuroSCORE II (C-index 0.66, 95% CI 0.52 to 0.79, p = 0.02) compared to the logistic EuroSCORE (C-index 0.63, 95% CI 0.51 to 0.76, p = 0.06) and STS (C-index 0.58, 95% CI 0.43 to 0.73, p = 0.23) score, without a significant difference among the 3 risk scores. Discrimination was slightly better in the transfemoral cohort compared to the transapical cohort with the 3 risk scores. In conclusion, EuroSCORE II and the STS score are better calibrated than the logistic EuroSCORE but have moderate discrimination for predicting 30-day mortality after TAVR.

Incidental papillary fibroelastoma multimodal: imaging and surgical decisions in 2 patients.

Papillary fibroelastoma is a rare, benign cardiac tumor typically found on the heart valves. It is usually discovered incidentally on echocardiography. The clinical presentation of cardiac papillary fibroelastoma varies from no symptoms to severe embolic sequelae. We report the incidental finding of papillary fibroelastoma in 2 patients. In each, we chose to excise the tumor. The relevant medical literature provides little guidance regarding whether to excise a small papillary fibroelastoma in an asymptomatic patient. Multimodal imaging, which we discuss in the context of our patients' cases, aids the cardiologist and cardiovascular surgeon in more accurately evaluating papillary fibroelastoma preoperatively.

De novo heterozygous desmoplakin mutations leading to Naxos-Carvajal disease.

STUDY/PRINCIPLES: Arrythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an autosomal-dominantly inherited disease caused by mutations in genes encoding desmosomal proteins and is characterised by fibrofatty replacement occurring predominantly in the right ventricle and can result in sudden cardiac death. Naxos and Carvajal syndrome, autosomal recessive forms of ARVC/D, are characterised by involvement of the right and/or left ventricle in association with palmoplantar keratoderma and woolly hair. The aim of the present study has been to screen for mutations in the desmosomal protein genes of two unrelated patients with Naxos-Carvajal syndrome. METHODS AND RESULTS: Desmosomal protein genes were screened for mutations by polymerase chain reaction as well as direct sequencing approach. In each patient we identified a single heterozygous de novo mutation in the desmoplakin gene DSP, p.Leu583Pro and p.Thr564Ile, leading to severe combined cardiac/dermatological and cardiac/dermatological/dental phenotypes. The DSP missense mutations are localised in the N terminal domain of desmoplakin. CONCLUSION: The identified variations in DSP involve highly conserved residues. Moreover, the variations are de novo mutations and they are localised in critical protein domains that appear to be mutation hot spots. We assume that these heterozygous variations are causal for the mixed Naxos-Carvajal syndrome phenotype in the screened patients.

Arteriogenic therapy by intramyocardial sustained delivery of a novel growth factor combination prevents chronic heart failure.

BACKGROUND: Therapeutic angiogenesis is a promising approach for the treatment of cardiovascular diseases, including myocardial infarction and chronic heart failure. We aimed to improve proangiogenic therapies by identifying novel arteriogenic growth factor combinations, developing injectable delivery systems for spatiotemporally controlled growth factor release, and evaluating functional consequences of targeted intramyocardial growth factor delivery in chronic heart failure. METHODS AND RESULTS: First, we observed that fibroblast growth factor and hepatocyte growth factor synergistically stimulate vascular cell migration and proliferation in vitro. Using 2 in vivo angiogenesis assays (n=5 mice per group), we found that the growth factor combination results in a more potent and durable angiogenic response than either growth factor used alone. Furthermore, we determined that the molecular mechanisms involve potentiation of Akt and mitogen-activated protein kinase signal transduction pathways, as well as upregulation of angiogenic growth factor receptors. Next, we developed crosslinked albumin-alginate microcapsules that sequentially release fibroblast growth factor-2 and hepatocyte growth factor. Finally, in a rat model of chronic heart failure induced by coronary ligation (n=14 to 15 rats per group), we found that intramyocardial slow release of fibroblast growth factor-2 with hepatocyte growth factor potently stimulates angiogenesis and arteriogenesis and prevents cardiac hypertrophy and fibrosis, as determined by immunohistochemistry, leading to improved cardiac perfusion after 3 months, as shown by magnetic resonance imaging. These multiple beneficial effects resulted in reduced adverse cardiac remodeling and improved left ventricular function, as revealed by echocardiography. CONCLUSION: Our data showing the selective advantage of using fibroblast growth factor-2 together with hepatocyte growth factor suggest that this growth factor combination may constitute an efficient novel treatment for chronic heart failure.

Complete pacemaker lead fracture potentially due to intra-cardiac mass.

Seven years after the implantation of a dual-chamber pacemaker, a 74-year-old woman was referred for syncope. Chest X-ray revealed that the ventricular lead was completely broken near the tricuspid valve. Fluoroscopy and transthoracic echocardiography found a calcified mass, moving with the proximal part of the ventricular lead. Anatomopathology of the atrial tumour remained unknown. Surgery was considered too invasive a technique to be performed in our patient, who was suffering from dementia.